Ethnic disparities in medication adherence? A systematic review examining the association between ethnicity and antidiabetic medication adherence

Objectives Adherence to prescribed medication is an essential component of diabetes management to obtain optimal outcomes. Understanding the relationship between medication adherence and ethnicity is key to optimising treatment for all people with different chronic illnesses, including those with diabetes. The aim of this review is to examine whether the adherence to antidiabetic medications differed by ethnicity among people with diabetes. Methods A systematic review was conducted of studies reporting adherence to antidiabetic medication amongst people from different ethnic groups. MEDLINE, Embase, CINAHL, and PsycINFO were searched from their inception to June 2022 for quantitative studies with a specific focus on studies assessing adherence to antidiabetic medications (PROSPERO: CRD42021278392). The Joanna Briggs Institute critical appraisal checklist and a second checklist designed for studies using retrospective databases were used to assess study quality. A narrative synthesis approach was used to summarize the results based on the medication adherence measures. Results Of 17,410 citations screened, 41 studies that included observational retrospective database research and cross-sectional studies were selected, each of which involved diverse ethnic groups from different settings. This review identified a difference in the adherence to antidiabetic medications by ethnicity in 38 studies, despite adjustment for several confounding variables that may otherwise explain these differences. Conclusion This review revealed that adherence to antidiabetic medication differed by ethnicity. Further research is needed to explore the ethnicity-related factors that may provide an explanation for these disparities.

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Our updated statement is as follows: "All data related to this study are included in this published article (and its supplementary information files. "

Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly.
Thank you for the reminder. We included captions for the supporting information files at the end of our manuscript and have updated the in-text citations to match accordingly.
[Page:25, Line:619-623]: "Supporting information S1 Table. PRISMA 2020 checklist S1 Text. Database search terms S2 Thank you for the comment. We agree that adherence is a complex sociological phenomenon and heavily influenced by numerous clinical, social and pharmacological factors, and we believe that ethnicity is also one of these factors.
We chose not to pool our data quantitatively in the form of a meta-analysis due to the wide variability between the between individual observational studies, including different settings/country of residence, types of medicines, adherence measures, as well as the different clinical and social characteristics of the population. Also, in addition, different studies used different analytical approaches and adjusted for different confounders.
We therefore accept that ascertaining specific reasons for variation in adherence is challenging, thus it would be inappropriate to provide a pooled quantitative value in terms of ethnicity for who is, or who is not, likely to be adherent to their antidiabetic medication.
However, we also feel that ethnicity of a patient could still have an important role in a patient being adherent to their medicines. Rather than employ a metaanalytical approach, we were interested in establishing if there were differences in medicines adherence between ethnicities across a population.
Despite there being many primary research studies reporting this information, there has been no systematic summary of this information. As such, we decided a narrative synthesis approach would be the best method to meet our objectives.
We believe there is value in narratively synthesising what exists in the literature with describing the limitations and our view; it is clear that there is a demonstrable influence from ethnicity, albeit the exact quantification of the size of this influence may not be possible to measure, given the wide variability of the studies.
Patients from minority ethnic populations, who are socioeconomically disadvantaged almost always have poorer outcomes that their white counterparts. This is something that needs to be urgently addressed within our healthcare systems and we believe this synthesis will help define some of these challenges.

2-Authors should briefly define the various adherence measures.
Thanks for the suggestion. We have now provided a summary definition of the various adherence measures as follows:  [2]. Subjective measurements include methods needing either patient self-report or health care professional evaluations of adherence to prescribed medicines [2]. On the other hand, objective measurements involve counting of pills, electronic monitoring, analysis of the secondary database [2]. "

3-How do individual studies (and your review) deal with mixed ethnicity?
Thanks for your question.
For individual studies, only six reported details about dealing with people from mixed race/ethnicity [3][4][5][6][7][8], three of them included people from a mixed ethnicity [3,5,8]. Two of these studies reported mixed ethnicity based on the Office of National Statistics official UK ethnicity categories [5,8] and the third included people from mixed ethnicity in Hawaii based on self-reported data from member surveys [3].
For the remaining three studies, they excluded people from mixed ethnicity from the analysis [4,6,7].
For this review: Mixed ethnicity was reported according to what was reported in each individual study.

2-4-
In the results section, the authors often report "other races" and in some cases (eg lines 253-255) a difference of some ethnic groups is reported without reporting the comparison group.
In the results section, the authors often report "other races", which should be reported in full. Furthermore, in some cases (e.g. page 16, lines 253-256), a difference of some ethnic groups is reported without mentioning the comparative group.

3-
• (In the results section, the authors often report "other races") Thank you for pointing this out.
We agree that "other races" should be reported in full. However, "other races" are reported in this review according to what is reported in each individual study.

• (in some cases (eg lines 253-255) a difference of some ethnic groups is reported without reporting the comparison group.)
Thank you very much for the reminder. We have made revisions accordingly as follows: [Page:16, Line:269]: "Of these, seven studies indicated that people from Black, Hispanic, and Asian ethnicity were more likely to be non-adherent to antidiabetic medications than people of White ethnicity, and these findings were statistically significant in four studies. "

(In some cases (e.g. page 16, lines 253-256), a difference of some ethnic groups is reported without mentioning the comparative group.)
[Page:17, Line:296]: "The authors found that the adherence varied significantly by ethnicity, and the odds of adherence were lower for people of Black ethnicity than those of White and Hispanic ethnicity. " Also, we went through the results to make sure that the difference between some ethnic groups was reported with reporting the comparison group. Therefore, we have revised another sentence as follows: [Page:17, Line:308-309]: "Lopez and colleagues and Osborn and colleagues demonstrated a significant association between increased adherence to antidiabetic medications and White ethnicity compared to African American, Hispanic, Asian, and American Indian ethnic groups. "

3-Response to reviewer #2
Reviewer #2 comments Authors' Response Thank you very much for the supportive comment.
2-on page 6, the authors correctly state that they prefer the term "ethnicity" to "race". This might be preferable not only for semantic reason, but also because, giving that ethnicity encompasses those cultural and geographical characteristics that are more likely to account for differences in medication adherence. In other words, it is also more technically sound to use the term ethnicity in this context because it ideally allows to take more confounders into account. This should be better reported in the methods section.
We very much appreciate this comment and agree that ethnicity encompasses cultural and geographical characteristics that are more likely to account for differences in medication adherence, we revised in the method section as follows: [Page:6, Line:164-172]: "While some included studies use the term 'race', we prefer the term 'ethnicity', which is defined in this review according to Senior and Bhopal 'implies one or more of the following: shared origins or social background; shared culture and traditions that are distinctive, maintained between generations, and lead to a sense of identity and group; and a common language or religious tradition [9].' The term of 'ethnicity' is preferred as it encompasses cultural and geographical characteristics, which will allows to take more confounders into account that are more likely to account for differences in medication adherence. For the included studies, we used labels provided by the authors of the original studies. "

3-
The discussion could might be better elaborated. The main differences between ethnicities are not summarized in a narrative statement in the discussion, although they are thoroughly reported in Table 1.
Thank you for your suggestion. Due to the limitation of variation between included observational studies in terms of setting, sample size, type of drugs, number of centres, study design, adherence measures, inclusion and exclusion criteria, clinical and social characteristics of the population, comorbidities, adjusted confounders as highlighted by reviewer#1, we cannot pull the data from table 1 and give a summary of differences by each ethnic group, so we added an overall difference between ethnicities as follows: [Page:18, Line:323-326]: "This variation was statistically significant in 34 studies out of 41 included studies and was overall observed between people from ethnic minorities and the majority populations in each specific study setting. Moreover, it is reported when adherence was measured using various measurement methods. "

4-were there any important differences between glucose-lowering classes?
Is there any factor that makes different ethnicities prefer oral antidiabetics rather than injectables?
Thank you for this question. It would have been interesting to explore this aspect. However, in the case of our review, it is out of scope for our research question as we mainly focus on exploring whether general adherence to antidiabetic medication varied by ethnicity. This suggestion has been noted for future research ideas.

5-access to diabetes medication in the world cannot be ignored, please refer to the latest WHO report https://www.who.int/publications/i/item/9789241565257
Thank you for pointing this out. We agree that access to diabetes medication is an important determinant of adherence. However, the majority of studies (33 out of 41) in this review are retrospective database studies, which analyse the data of people who already have access to their antidiabetic medications.
We do accept that this is something that needs to be investigated but would be part of a different review in our opinion. The question of ability to pay for medicines would also be very relevant in this space, especially in certain healthcare systems around the world Thank you for this suggestion. It would be interesting to explore this aspect in future work. However, in our review, it seems slightly out of scope as we mainly focus on exploring whether adherence to antidiabetic medication varied by ethnicity in people with type 1 or type 2 diabetes. Thank you for giving this study as an example. However, this study did not meet the inclusion criteria for our systematic review, as it only included one ethnic group; the eligibility criteria for our systematic review specified that the study must have more than one ethnic group in order to reflect on comparisons.
7-it is certainly true that the cause of these disparities should be better investigated in future research, however that is not the only necessity and is also already partly known. The authors should speculate on possible tools for identifying adherence issues and improving it across different ethnic groups.
Thank you for this suggestion. We added it to discussion section as follows: [Page:20, Line:374-376]: "Therefore, developing a cross-culturally validated adherence measure in future work may help identify and improve adherence issues across different ethnic groups. "